Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration

Yue Tian,Zhen Chen,Yuqin Shen,Yawei Wang,Lijing Wang,Tong Ding,Hongbing Lin,Huishan Chen,Xuetao Zhao,Peipei Zhang

doi:10.1186/s12967-021-03125-5

Abstract

Periodontitis is a chronic inflammatory disease that leads to the destruction of both soft and hard periodontal tissues. Complete periodontal regeneration in clinics using the currently available treatment approaches is still a challenge. Mesenchymal stem cells (MSCs) have shown promising potential to regenerate periodontal tissue in various preclinical and clinical studies. The poor survival rate of MSCs during in vivo transplantation and host immunogenic reaction towards MSCs are the main drawbacks of direct use of MSCs in periodontal tissue regeneration. Autologous MSCs have limited sources and possess patient morbidity during harvesting. Direct use of allogenic MSCs could induce host immune reaction. Therefore, the MSC-based indirect treatment approach could be beneficial for periodontal regeneration in clinics. MSC culture conditioned medium (CM) contains secretomes that had shown immunomodulatory and tissue regenerative potential in pre-clinical and clinical studies. MSC-CM contains a cocktail of growth factors, cytokines, chemokines, enzymes, and exosomes, extracellular vesicles, etc. MSC-CM-based indirect treatment has the potential to eliminate the drawbacks of direct use of MSCs for periodontal tissue regeneration. MSC-CM holds the tremendous potential of bench-to-bed translation in periodontal regeneration applications. This review focuses on the accumulating evidence indicating the therapeutic potential of the MSC-CM in periodontal regeneration-related pre-clinical and clinical studies. Recent advances on MSC-CM-based periodontal regeneration, existing challenges, and prospects are well summarized as guidance to improve the effectiveness of MSC-CM on periodontal regeneration in clinics.

Highlights

Periodontitis is a complicated chronic inflammatory oral disease, which is globally prevalent and has direct involvement of vast oral microbiome, oral tissues and immune cells [1, 2]
Stem cell-based periodontal regeneration is currently at the center of attention [18]. Different cell types such as bone marrow Mesenchymal stem cells (MSCs) (BMSCs), periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSC) are key stem cells used in stem cell-based periodontal regeneration [19]
We summarized the regeneration of periodontal tissue by conditioned medium (CM) from different MSC sources, including BMSCs, PDLSCs, GMDCs, APTGs, DFGs, ADMPCs, adipose-derived mesenchymal stem cells (ASCs), osteoblast, etc

Summary

Background

Periodontitis is a complicated chronic inflammatory oral disease, which is globally prevalent and has direct involvement of vast oral microbiome, oral tissues and immune cells [1, 2]. Two review articles by Park CH et al and Xu et al had well summarized recent advances on exogenous stem cell-based therapies for periodontal tissue regeneration [19, 70]. Cytokine antibody array analysis revealed 201 unique gene products in human embryonic stem cell-derived MSC-CM (hESC-MSC-CM) (Fig. 3) These growth factors significantly drive the biological processes of metabolism, defense response, and tissue regeneration [75]. Reports from literature had unraveled the various biological activities of MSC-CM, including, osteoinductive, angioinductive, chemotactic, immunomodulatory, and cell growth and differentiation (Fig. 4) These entire biological activities of MSC-CM could facilitate the periodontal tissue regeneration. VEGF [103] and FGF-2[104] in MSC-CM are proposed to be the main signaling factors that induce bone regeneration by promoting angiogenesis.

Healthy or inflamed PDLSCs ‘Inflamed’ PDLSCs

Findings

Conclusion